HIV Neurobehavioral Research Program.
Department of Psychiatry.
AIDS. 2018 Sep 10;32(14):2005-2015. doi: 10.1097/QAD.0000000000001927.
Antiretroviral therapy (ART) is currently recommended for all persons living with HIV (PLWH), regardless of their CD4 T-cell count, and should be continued throughout life. Nonetheless, vigilance of the safety of ART, including its neurotoxicity, must continue. We hypothesized that use of certain ART drugs might be associated with aging-related cerebral degenerative changes among PLWH.
Clinicopathological study of PLWH who were using ART drugs at the last clinical assessment.
Using multivariable logistic regression, we tested associations between use of each specific ART drug (with reference to use of other ART drugs) and cerebral degenerative changes including neuronal phospho-tau lesions, β-amyloid plaque deposition, microgliosis, and astrogliosis in the frontal cortex and putamen (immunohistochemistry), as well as cerebral small vessel disease (CSVD) in the forebrain white matter (standard histopathology), with relevant covariates being taken into account. The Bonferroni adjustment was applied.
Darunavir use was associated with higher likelihood of neuronal phospho-tau lesions in the putamen [odds ratio (OR) 15.33, n = 93, P = 0.005]. Ritonavir use was associated with marked microgliosis in the putamen (OR 4.96, n = 101, P = 0.023). On the other hand, use of tenofovir disoproxil fumarate was associated with lower likelihood of β-amyloid plaque deposition in the frontal cortex (OR 0.13, n = 102, P = 0.012). There was a trend toward an association between emtricitabine use and CSVD (OR 13.64, n = 75, P = 0.099).
Our findings suggest that PLWH treated with darunavir and ritonavir may be at increased risk of aging-related cerebral degenerative changes.
抗逆转录病毒疗法（ART）目前推荐用于所有艾滋病毒感染者（PLWH），无论其 CD4 T 细胞计数如何，并且应终身持续。尽管如此，仍必须继续关注 ART 的安全性，包括其神经毒性。我们假设，某些 ART 药物的使用可能与 PLWH 与年龄相关的大脑退行性变化有关。
在最后一次临床评估时正在使用 ART 药物的 PLWH 的临床病理研究。
使用多变量逻辑回归，我们测试了使用每种特定的 ART 药物（与使用其他 ART 药物相比）与大脑退行性变化之间的关联，包括大脑前额皮质和壳核中的神经元磷酸化 tau 病变、β-淀粉样斑块沉积、小胶质细胞增生和星形胶质细胞增生（免疫组织化学），以及大脑前脑白质中的小血管疾病（CSVD）（标准组织病理学），并考虑了相关的协变量。应用了 Bonferroni 调整。
达芦那韦的使用与壳核中的神经元磷酸化 tau 病变的可能性增加有关（比值比[OR] 15.33，n=93，P=0.005）。利托那韦的使用与壳核中的明显小胶质细胞增生有关（OR 4.96，n=101，P=0.023）。另一方面，使用富马酸替诺福韦二吡呋酯与大脑前额皮质中β-淀粉样斑块沉积的可能性降低有关（OR 0.13，n=102，P=0.012）。恩曲他滨的使用与 CSVD 之间存在关联的趋势（OR 13.64，n=75，P=0.099）。
我们的研究结果表明，接受达芦那韦和利托那韦治疗的 PLWH 可能面临与年龄相关的大脑退行性变化的风险增加。
